Abstract:We highlight mechanical stretching and bending of membranes and the importance of membrane deformations in the analysis of swelling dynamics of biological systems, including cells and subcellular organelles. Membrane deformation upon swelling generates tensile stress and internal pressure, contributing to volume changes in biological systems. Therefore, in addition to physical (internal/external) and chemical factors, mechanical properties of the membranes should be considered in modeling analysis of cellular … Show more
“…So, it is unclear to what degree macromolecular breakdown would draw in water. Alternately, the role of membrane stretching and/or increased hydrostatic pressure on swelling dynamics is difficult to model, but it has been proposed that increased intracellular pressure from the stretched plasma membrane could reduce water influx [ 71 ], which might stabilize the grossly swollen state of cell bodies and dendrites. Fig.…”
Section: Brain Cell Swelling and Ischemiamentioning
An acute reduction in plasma osmolality causes rapid uptake of water by astrocytes but not by neurons, whereas both cell types swell as a consequence of lost blood flow (ischemia). Either hypoosmolality or ischemia can displace the brain downwards, potentially causing death. However, these disorders are fundamentally different at the cellular level. Astrocytes osmotically swell or shrink because they express functional water channels (aquaporins), whereas neurons lack functional aquaporins and thus maintain their volume. Yet both neurons and astrocytes immediately swell when blood flow to the brain is compromised (cytotoxic edema) as following stroke onset, sudden cardiac arrest, or traumatic brain injury. In each situation, neuronal swelling is the direct result of spreading depolarization (SD) generated when the ATP-dependent sodium/potassium ATPase (the Na+/K+ pump) is compromised. The simple, and incorrect, textbook explanation for neuronal swelling is that increased Na+ influx passively draws Cl− into the cell, with water following by osmosis via some unknown conduit. We first review the strong evidence that mammalian neurons resist volume change during acute osmotic stress. We then contrast this with their dramatic swelling during ischemia. Counter-intuitively, recent research argues that ischemic swelling of neurons is non-osmotic, involving ion/water cotransporters as well as at least one known amino acid water pump. While incompletely understood, these mechanisms argue against the dogma that neuronal swelling involves water uptake driven by an osmotic gradient with aquaporins as the conduit. Promoting clinical recovery from neuronal cytotoxic edema evoked by spreading depolarizations requires a far better understanding of molecular water pumps and ion/water cotransporters that act to rebalance water shifts during brain ischemia.
“…So, it is unclear to what degree macromolecular breakdown would draw in water. Alternately, the role of membrane stretching and/or increased hydrostatic pressure on swelling dynamics is difficult to model, but it has been proposed that increased intracellular pressure from the stretched plasma membrane could reduce water influx [ 71 ], which might stabilize the grossly swollen state of cell bodies and dendrites. Fig.…”
Section: Brain Cell Swelling and Ischemiamentioning
An acute reduction in plasma osmolality causes rapid uptake of water by astrocytes but not by neurons, whereas both cell types swell as a consequence of lost blood flow (ischemia). Either hypoosmolality or ischemia can displace the brain downwards, potentially causing death. However, these disorders are fundamentally different at the cellular level. Astrocytes osmotically swell or shrink because they express functional water channels (aquaporins), whereas neurons lack functional aquaporins and thus maintain their volume. Yet both neurons and astrocytes immediately swell when blood flow to the brain is compromised (cytotoxic edema) as following stroke onset, sudden cardiac arrest, or traumatic brain injury. In each situation, neuronal swelling is the direct result of spreading depolarization (SD) generated when the ATP-dependent sodium/potassium ATPase (the Na+/K+ pump) is compromised. The simple, and incorrect, textbook explanation for neuronal swelling is that increased Na+ influx passively draws Cl− into the cell, with water following by osmosis via some unknown conduit. We first review the strong evidence that mammalian neurons resist volume change during acute osmotic stress. We then contrast this with their dramatic swelling during ischemia. Counter-intuitively, recent research argues that ischemic swelling of neurons is non-osmotic, involving ion/water cotransporters as well as at least one known amino acid water pump. While incompletely understood, these mechanisms argue against the dogma that neuronal swelling involves water uptake driven by an osmotic gradient with aquaporins as the conduit. Promoting clinical recovery from neuronal cytotoxic edema evoked by spreading depolarizations requires a far better understanding of molecular water pumps and ion/water cotransporters that act to rebalance water shifts during brain ischemia.
“…From the theoretical side, several mathematical models and continuum mechanic simulations have been developed to study mitochondrial mechanics. ,,− Urchin developed an elastic-mathematical theory to calculate the Young’s modulus and stresses of cells and mitochondria during the swelling process . Theoretical models based on the Euler–Lagrange equation have been developed to describe the mechanical properties, including bending and stretching of cell and mitochondrial membranes. − Various kinetic models for simulation and prediction of in vivo mitochondrial swelling have been proposed, which contribute to our understanding of the mechanisms of metabolic and functional changes in the cell under physiological and pathological conditions . Hydrodynamic simulations using the finite element method have also been performed to estimate the mechanical properties of suspended mitochondria .…”
“…It is understood that DVE cells are induced at the distal tip as the embryo grows and elongates, distancing the distal cells of the VE from repressive BMP signals emanating from the ExE (Mesnard et al 2006;Rodriguez et al 2005). Nevertheless, as DVE cells are positioned at the distal-tip of the cylinder-shaped VE, the region with the highest tissue curvature, these cells may also be subject to increased mechanical stress (Helfrich 1973;Khairy et al 2018;Khmelinskii and Makarov 2020). As mechanical cues can affect cell fate decisions and cell behaviour (De Belly et al 2022;Discher et al 2009), it is unclear whether the columnar morphology and behaviour of the migratory DVE cells is due to biomechanical differences imposed by the curvature of the VE tissue, or autonomously controlled.…”
Distal Visceral Endoderm (DVE) cells show a stereotypic unidirectional migration essential for correct orientation of the anterior-posterior axis. They migrate within a simple epithelium, the Visceral Endoderm (VE). It is unknown how DVE cells negotiate their way amongst the surrounding VE cells, what determines the bounds of DVE migration within the VE, and the relative contributions of different cell behaviours to this migration. To address these questions, we used lightsheet microscopy to generate a multi-embryo, single-cell resolution, longitudinal dataset of cell behaviour and morphology. We developed a machine learning based pipeline to segment cells and a data-informed systematic computational framework to extract and compare select morphological, behavioural and molecular parameters of all VE cells in a unified coordinate space. Unbiased clustering of this single-cell phenomic dataset reveals considerable patterned phenotypic heterogeneity within the VE and a previously unknown sub-grouping within the DVE. While migrating, DVE cells retain regular morphology, do not exchange neighbours and are crowded, all hallmarks of the jammed state. In contrast, VE cells immediately ahead of them deform and undergo neighbour exchange. We show that DVE cells are characterised by higher levels of apical F-actin and elevated tension relative to the VE cells immediately ahead of them through which they migrate, but stop migrating upon reaching a region of the VE with matching elevated tension. Lefty1 mutants, known to show abnormal over-migration of DVE cells, show disruption to this patterned tension in the VE. Our findings provide novel insights into the control of cell behaviour during the remodelling of curved epithelia, indicating that the collective migration of sub-sets of cells can be circumscribed by modulating the mechanical properties of surrounding cells and that migrating cells in this context remain as a jammed solid flock, with surrounding cells facilitating their movement by becoming unjammed.
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